cholecalciferol and Anemia--Refractory

Refractory anemias and the myelodysplastic syndromes are a group of hematopoietic stem cell disorders characterized by ineffective and dysplastic hematopoiesis, leading to persistent peripheral cytopenias. Patients also have an increased risk of transformation to acute myelogenous leukemia. Since defective cellular maturation is the central pathogenetic feature, improved differentiation may result in correction of neutropenia and thrombocytopenia. Clinical trials using retinoic acid and vitamin D3 analogues are not satisfactory and only small numbers of patients may benefit from receiving them. In view of the absence of other effective treatment, future studies should be directed to the combined use of differentiating agents with hematopoietic growth factors and to the identification of new compounds with greater differentiating ability and less toxicity.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Animals; Cholecalciferol; Female; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Tretinoin

In a cooperative trial, 99 patients with refractory anemias were treated according to a standard protocol consisting of successive administration of prednisolone (PSL), 1 alpha hydroxyvitamin D3 (D3) and androgens. The primary objective of this protocol was to ameliorate peripheral cytopenia and to assess the value of the 3 drugs, claimed to be of some value, in the management of patients with refractory anemias. In principle, patients were initially treated with oral PSL 40-60 mg/day. Patients not responding to PSL within 4 weeks had an 8-week trial of D3 starting with 1 microgram/day, increasing to 3 micrograms/day. Those not responding to either of the two were given AS. Although the number of evaluable courses is limited as yet for each drug, the preliminary results suggest 1) a slight to moderate increase in hemoglobin in 20-25% of patients on PSL, 2) a partial increase in granulocyte and/or platelets and a reduction of marrow blasts in 10-20% of patients during the administration of D3 and 3) the effects are poorer in cases of severe cytopenia. In addition, the improvement was mostly transient. The treatment was well tolerated in the majority of patients.

Topics: Administration, Oral; Androgens; Androstanols; Anemia, Refractory; Cholecalciferol; Drug Administration Schedule; Drug Therapy, Combination; Humans; Oxymetholone; Prednisolone

We have examined the efficacy of various drugs in 44 patients with MDS and found the different effectiveness which depends on the type of MDS. Namely, RA appears to respond to steroid hormone, androgen, and/or vitamin D3, regardless of single or combined use. In particular, it is obvious in androgen, and as our previous reports, high content of acidic ferritin in RBC with RA have changed to more basic ones by treatment with androgen. On the contrary, these drugs were not effective on RAEB, RAEB-T, and CMML. A long-term observation is needed to determine whether the prolonged or decreased occurrence of leukemia could be obtained in the effective cases with RA. Most of the cases who did not develop overt leukemia during this study died of bleeding or infections due to thrombocytopenia or leukocytopenia, thus indicating that supportive therapies are important in patients with MDS. Since it has recently been reported that recombinant G-CSF or GM-CSF is helpful to increase the number of leucocyte and to enhance their functional recovery in MDS, these factors may be powerful agents against infections when they are carefully used with regard to the activation of leukemic clones.

Topics: Adult; Aged; Androgens; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Blast Crisis; Cholecalciferol; Chromosome Aberrations; Cytarabine; Female; Humans; Leukemia, Myeloid; Male; Middle Aged; Preleukemia; Prognosis